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Biomedical subjects

H Simpson

Publications and source records attributed to H Simpson.

At least 19 recordsLinked to original sources
PubMed2003

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Diamorphine or morphine for ischaemic cardiac chest pain.

A short cut review was carried out to establish whether morphine is better than diamorphine at allieviating chest pain after an acute myocardial infarction. Altogether 66 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Analgesics, Opioid↗
PubMed2002

Current methods of transfer of young people with Type 1 diabetes to adult services.

AIMS: To determine the efficacy and patient perception of various transfer procedures from paediatric to adult diabetes services. METHODS: Comparison between four districts in the Oxford Region employing different transfer methods, by retrospective study of case records and interviews of patients recently transferred from paediatric diabetes clinics. The main outcome measures were age at transfer, clinic attendance rates, HbA1c measurements and questionnaire responses. RESULTS: Two hundred and twenty-nine subjects (57% males) > 18 years old in 1998 and diagnosed with Type 1 diabetes < 16 years of age between 1985 and 1995, identified from the regional diabetes register. The notes audit was completed for 222 (97%) and 164 (72%) were interviewed by a single research nurse. Mean age at transfer was 17.9 years (range 13.3-22.4 years). Few young people were lost to follow-up at the point of transfer. There was a high rate of clinic attendance (at least 6 monthly) 2 years pretransfer (94%), but this declined to 57% 2 years post-transfer (P < 0.0005). There was large interdistrict variation in clinic attendance 2 years post-transfer (29% to 71%); higher rates were seen in districts where young people had the opportunity to meet the adult diabetes consultant prior to transfer. The importance of this opportunity was confirmed by questionnaire responses on interview. CONCLUSIONS: Adolescence is a vulnerable period for patients with diabetes. This regional survey demonstrated a marked decline in clinic attendance around the time of transition from paediatric to adult services. The reasons are complex, but mode of transfer may be an important factor.

Adolescent↗
PubMed2002

Transforming growth factor beta expression in human placenta and placental bed during early pregnancy.

Normal human pregnancy depends on physiological transformation of spiral arteries. Pre-eclampsia and fetal growth restriction are associated with impaired trophoblast invasion and spiral artery transformation. Recent data obtained from studies on placenta suggest that temporal changes in expression of TGF-beta3 play a key role in trophoblast invasion and that over-expression of TGF-beta3 in pre-eclampsia is responsible for inadequate trophoblast invasion. There are, however, no studies of specific TGF-betas in the placental bed throughout pregnancy although this is where the invasive trophoblast and spiral arteries are located. In this study we have used immunohistochemistry, Western blot analysis, ELISA and RT-PCR to examine the expression of TGF-beta1, TGF-beta2 and TGF-beta3 in placental bed biopsies and placentas from 7--19 weeks' gestation. The results show that TGF-beta1, 2 and 3 are expressed in the placenta throughout this time but the striking temporal changes in TGF-beta3 expression previously reported were not observed. Extravillous trophoblast within the placental bed expressed TGF-beta2 but not TGF-beta1 or TGF-beta3 while extracellular TGF-beta1 and cytoplasmic TGF-beta2 were detected in decidua. These data suggest that TGF-beta1 and TGF-beta2 but not TGF-beta3 may play a role in trophoblast invasion.

Adult↗
PubMed2001

Transforming growth factor-beta expression in human placenta and placental bed in third trimester normal pregnancy, preeclampsia, and fetal growth restriction.

Normal human pregnancy depends on physiological transformation of spiral arteries by invasive trophoblasts. Preeclampsia (PE) and fetal growth restriction (FGR) are associated with impaired trophoblast invasion and spiral artery transformation. Recent studies have suggested that transforming growth factor (TGF)-beta3 is overexpressed in the placenta of PE patients and that this may be responsible for failed trophoblast invasion. There are, however, no studies on TGF-betas in the placenta in FGR or in the placental bed in PE or FGR. In this study we have used immunohistochemistry, Western blot analysis, and enzyme-linked immunosorbent assay to examine the expression of TGF-beta1, TGF-beta2, and TGF-beta3 in placenta and placental bed of pregnancies complicated by PE and FGR and matched control pregnancies. The results show that TGF-beta1, -beta2, and -beta3 are not expressed in villous trophoblasts but are present within the placenta. TGF-beta1, -beta2, and, to a much lesser extent, TGF-beta3 were present within the placental bed but only TGF-beta2 was present in extravillous trophoblast. No changes in expression of either isoform were found in placenta or placental bed in PE or FGR compared with normal pregnancy. These data are not consistent with overexpression of TGF-beta3 being responsible for failed trophoblast invasion in PE. Our findings suggest that the TGF-betas do not have a pathophysiological role in either PE or FGR.

Adult↗
PubMed2001

Rapid application fracture fixators - an evaluation of mechanical performance.

OBJECTIVE: This study evaluates the mechanical performance of the Pinless and Centrafix fixators for rapid application to tibial fractures in a disaster or battlefield scenario. DESIGN: Comparative study based on measurements made in the laboratory. BACKGROUND: The Pinless and Centrafix fixators may be considered for rapid application to stabilise fractures in emergency conditions without the aid of electrical equipment such as power drills for bone screw insertion or image intensifiers to facilitate bone alignment. METHODS: Stiffnesses, maximum service loads and fatigue strengths of the fixators were measured in the orientations of loading that correspond to walking and stretcher-bearing. These properties were compared with measurements on three conventional fixators, the AO, Shearer and Triax. RESULTS: The Centrafix stiffnesses were 31 N/mm (axial), 1 N/ degrees (torsional shear), 0.4 N/ degrees (coronal plane bending), 4 N/ degrees (sagittal plane bending) and 11 N/mm (transverse shear) and strengths were 95 N (axial) and 1.9 Nm (bending). Corresponding Pinless stiffnesses were 43 N/mm, 0.7 N/ degrees, 0.3 N/ degrees, 8 N/ degrees and 50 N/mm, and strength was 55 N (axial). CONCLUSIONS: The stiffness and strength of both rapid application fixators in simulated walking was judged to be low, and additionally the stiffness and strength of the Centrafix in simulated stretcher-bearing was judged to be low. RELEVANCE: The Pinless is not recommended for weight-bearing subjects with unstable fractures. The Centrafix is not recommended for stretcher-bearing or weight-bearing with unstable fractures.

Biomechanical Phenomena↗
PubMed2001

Muscle fibre damage and regeneration resulting from surgical limb distraction.

Using an animal model of limb distraction, the extent of muscle fibre damage and atrophy resulting from distraction at two different rates (1.3 or 3.0 mm day(-1)) was investigated. It was found that at the high rate of distraction there was a significantly greater loss of range of joint movement and more muscle fibre atrophy and fibre damage than at the low rate. Muscle fibre damage is usually followed by regeneration. This involves the expression of the neonatal form of myosin heavy chain, which can therefore be used as an indicator of regeneration. It was found that whilst many more fibres showed evidence of damage at the high compared to the low rate, the number of fibres expressing neonatal myosin was significantly reduced, indicating the presence of a population of fibres which was undergoing degeneration without subsequent regeneration. Thus it would appear that beyond a certain rate of distraction, regeneration may be insufficient to replace contractile material damaged by overstretching. It is suggested that these fibres are replaced with connective tissue. This process may contribute to the muscle weakness and loss of range of joint movement which sometimes accompanies limb distraction procedures.

Animals↗
PubMed2001

Response of the physis to leg lengthening.

UNLABELLED: The physeal response to limb lengthening by callotasis was investigated in an animal model by measuring 1) the growth rate using an oxytetracycline labelling technique, 2) histomorphological changes, and 3) proliferative cellular activity using bromodeoxyuridine. An osteotomy without lengthening stimulated growth at the physis. At 20% lengthening, regardless of the rate of distraction, no significant changes were detected. However, the growth rate was drastically reduced after 30% or more of lengthening and in 50% of cases there was evidence of premature closure of the distal growth plate. CLINICAL RELEVANCE: Caution should be exercised in carrying out high percentages of lengthening of children's bones.

Animals↗
PubMed2000

Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity.

AIMS/HYPOTHESIS: Phosphoinositide 3-kinase (PI 3K) plays a central part in the mediation of insulin-stimulated glucose disposal. No genetic studies of this enzyme in human syndromes of severe insulin resistance have been previously reported. METHODS: Phosphoinositide 3-kinase p85 alpha regulatory subunit cDNA was examined in 20 subjects with syndromes of severe insulin resistance by single strand conformational polymorphism and restriction fragment length polymorphism analyses. Insulin-stimulated phosphoinositide 3-kinase activity and recruitment into phosphotyrosine complexes of variants of p85 alpha were studied in transiently transfected HEK293 cells. Phosphopeptide binding characteristics of wild-type and mutant p85 alpha-GST fusion proteins were examined by surface plasmon resonance. RESULTS: The common p85 alpha variant, Met326I1e, was identified in 9 of the 20 subjects. Functional studies of the Met326Ile variant showed it to have equivalent insulin-stimulated lipid kinase activity and phosphotyrosine recruitment as wild-type p85 alpha. A novel heterozygous mutation, Arg409Gln, was detected in one subject. Within the proband's family, carriers of the mutation had a higher median fasting plasma insulin (218 pmol/l) compared with wild-type relatives (72 mol/l) (n = 8 subjects, p = 0.06). The Arg409Gln p85 alpha subunit was associated with lower insulin-stimulated phosphoinositide 3-kinase activity compared with wild-type (mean reduction 15%, p < 0.05, n = 5). The recruitment of Arg409Gln p85 alpha into phosphotyrosine complexes was not significantly impaired. GST fusion proteins of wild-type and mutant p85 alpha showed identical binding to phosphopeptides in surface plasmon resonance studies. CONCLUSION/INTERPRETATION: Mutations in p85 alpha are uncommon in subjects with syndromes of severe insulin resistance. The Met326Ile p85 alpha variant appears to have no functional effect on the insulin-stimulated phosphoinositide 3-kinase activity. The impaired phosphoinositide 3-kinase activity of the Arg409Gln mutant suggests that it could contribute to the insulin resistance seen in this family.

Adult↗
PubMed2000

No objective benefit from steroids inhaled via a spacer in infants recovering from bronchiolitis.

A double-blind randomized placebo-controlled trial was conducted to investigate the efficacy of 3 months' inhaled steroids delivered via a spacer device with face mask attachment to infants recovering from bronchiolitis. Forty-eight previously healthy infants recovering from their first documented episode of acute bronchiolitis were randomized to receive 150 microg fluticasone propionate (FP) b.i.d. or placebo delivered via the Babyhaler spacer. Longitudinal assessments were performed on seven occasions over 1 yr based on symptom diaries and health records, clinical examinations, overnight cough recordings and oxygen saturation readings. Lung function was measured 6 months after hospital discharge. Forty-three infants completed the trial (FP 21, placebo 22). There were no significant differences in the three objective end-points measured, recorded night cough, oxygen saturation and lung function test results. Symptom scores were low in both the FP and placebo groups with the absence of (0) or mild (1) symptoms > or =90% of the trial days. No statistical differences in symptom frequency, use of rescue respiratory medications or hospital admissions between treatment groups were found throughout the trial or follow-up periods. In conclusion, the use of inhaled fluticasone propionate in infants recovering from acute bronchiolitis cannot be recommended.

Administration, Inhalation↗
PubMed2000

Postprandial silent ischaemia following a fatty meal in patients with recently diagnosed coronary artery disease.

Silent myocardial ischaemia (SI) is recognised as an important prognostic factor in patients with coronary artery disease (CAD). Postprandial angina is related to severity of CAD. The effect of postprandial metabolic changes in the pathogenesis of SI is unclear. We studied the postprandial changes in glucose, insulin and triglyceride, and non-esterified fatty acids (NEFA) in relation to postprandial SI and exercise capacity, in patients with CAD. Forty elderly volunteers (63 +/- 1 years) mean age +/- s.e.m., with a history of angina were selected on the basis of a Rose questionnaire and a positive exercise stress test (modified Bruce protocol). The test meal contained 45% fat. The meal was consumed at 9.00 am and hourly blood samples were taken for glucose, insulin, triglyceride and NEFA. Continuous Holter monitoring for SI was conducted using a Spacelabs 2000 monitor. Twenty-five percent of the subjects had episodes of silent ischaemia. Postprandial glucose, insulin, triglyceride, and NEFA were not significantly different in the patients with SI (group 1, n = 10) compared with those without SI (group 2, n = 30). The mean exercise time was 6.1 +/- 0.8 min in group 1 compared with 6.8 +/- 0.5 minutes in group 2 (P = 0.48). The time to onset of ST depression during exercise test was also not significantly different in the two groups. The occurrence of postprandial SI cannot be related to changes in plasma levels of glucose, triglyceride, insulin, and NEFA. The explanation is not apparent from this study but may relate to a haemodynamic changes such as mesenteric steal. Journal of Human Hypertension (2000) 14, 391-394

Aged↗
PubMed2000

A locus for primary ciliary dyskinesia maps to chromosome 19q.

Primary ciliary dyskinesia is an autosomal recessive condition characterised by chronic sinusitis, bronchiectasis, and subfertility. Situs inversus occurs in 50% of cases (Kartagener syndrome). It has an estimated incidence of 1 in 20 000 live births. The clinical phenotype is caused by defective ciliary function associated with a range of ultrastructural abnormalities including absent dynein arms, absent radial spokes, and disturbed ciliary orientation. The molecular genetic basis is unknown. A genome scan was performed in five Arabic families. Using GENEHUNTER, a maximal multipoint lod score (HLOD) of 4.4 was obtained on chromosome 19q13.3-qter at alpha (proportion of linked families) = 0.7. A 15 cM critical region is defined by recombinations at D19S572 and D19S218. These data provide significant evidence for a PCD locus on chromosome 19q and confirm locus heterogeneity.

Adult↗
PubMed2000

Correction of complex lower limb deformities by the Ilizarov technique: An audit of complications.

This is an audit of complications resulting from correction of complex lower limb deformities by the Ilizarov technique. 33 patients (40 bone segments) were reviewed and divided into 4 groups according to the type of surgery carried out: limb lengthening and/or correction of deformity, bone or joint stabilisation, treatment of nonunion or bone defect, angular and/ or rotation correction. Most minor complications were fixator specific. Pin tract infections were almost universal but responded well to oral antibiotics and rarely resulted in osteomyelitis. Major complications were procedure specific and more common in those patients who underwent leg lengthening, treatment for nonunion and bone transport. There was also a high incidence of nerve injury as a result of acute angular deformity correction. Despite the high complication rate the Ilizarov technique remains an effective tool for complex lower limb reconstruction surgery.

Journal Article↗
PubMed2000

Treatment of growth hormone deficiency in adults.

In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.

Adult↗
PubMed2000

Risk factors for wheeze in the last 12 months in preschool children.

Most children with asthma develop their symptoms before the age of 5 years and many preschool wheezers continue to wheeze in the early school years. It is thus important to investigate the factors that predispose young children to wheeze. The objective of this study was to investigate the relevant environmental and family influences on recent wheeze (wheeze within the last 12 months) in preschool children. A cross-sectional study was conducted in five primary health clinics in the district of Kota Bharu from April to October 1998. Nurses from these clinics distributed Bahasa Malaysia questionnaires containing questions on asthma symptoms, environmental risk factors, family's social status and family history of atopy and wheeze to preschool children aged 1-5 years during their home visits. The respondents were parent(s) or carer(s) of the children. A total of 2,524 (87.7%) complete questionnaires were available for analysis of risk factors. One hundred and fifty six (6.2%) children had current wheeze. Significant risk factors associated with current wheeze were a family history of asthma (O.R. = 6.36, 95% C.I. = 4.45-9.09), neonatal hospital admission (O.R. = 2.38, 95% C.I. = 1.51 - 3.75), and a maternal (O.R. = 2.12, 95% C.I. = 1.31-3.41) or paternal (O.R. = 1.52, 95% C.I. = 0.95-2.43) history of allergic rhinitis. Among environmental factors examined, namely, household pets, carpeting in bedroom, use of fumigation mats, mosquito coils and aerosol insect repellents, maternal and paternal smoking, and air conditioning, none were associated with an increased risk of wheeze. In conclusion, the strongest association with current wheeze was a family history of asthma. Also significant were neonatal hospital admission and a history of allergic rhinitis in either the mother or father. None of the environmental factors studied were related to current wheeze in preschool children.

Asthma↗
PubMed2000

Prevalence of wheeze, night cough and doctor-diagnosed asthma in pre-school children in Kota Bharu.

While many studies of the prevalence of wheeze have been conducted in schoolchildren, there have been few in pre-school children. Most children with asthma develop symptoms before the age of 5 years and many pre-school wheezers continue to wheeze in the early school years. Among the latter, those children who continue to wheeze at school age have poorer lung function than those who don't. It is thus appropriate to enquire more fully about wheeze in this age-group where its incidence is high and its relation with asthma less well defined. The objective of this study was to investigate the prevalences of wheeze, night cough and doctor diagnosed asthma in pre-school children. A cross-sectional study was conducted in five primary health clinics in the district of Kota Bharu from April to October 1998. Nurses from these clinics distributed Bahasa Malaysia questionnaires containing questions on asthma symptoms to preschool children aged 1-5 years during their home visits. The respondents were parent(s) or carer(s) of the child. The response rate was 100% and a total of 2,878 responses were analysed. The prevalence of symptoms and doctor diagnosed asthma were as follows: ever wheezed 9.4% (95% confidence interval (CI) 8.3-10.4%); current wheeze 6.2% (95% CI 5.2 to 7.0%); night cough 10.2% (95% CI 9.1 to 11.4%); and doctor diagnosed asthma 7.1% (95% CI 6.2 to 8.0%). There were no significant differences in prevalence between males and females, or among age groups. The prevalence of night cough in children with no history of wheeze was 6.9%. The cumulative and current prevalences of wheeze were similar to, and those of night cough and doctor-diagnosed asthma significantly lower than, those reported for Kelantan schoolchildren. These findings provide a baseline for assessing future symptoms trends, and perhaps also the validity of diagnosing asthma in this age group.

Asthma↗
PubMed1999

Effect of rate of distraction on loss of range of joint movement, muscle stiffness, and intramuscular connective tissue content during surgical limb-lengthening: a study in the rabbit.

Surgical lengthening of limbs often results in loss of range of joint movement and this has been shown to be associated with an increase in passive tension and an increase in collagen content of the muscles. In this study, we have investigated the length/tension properties and the connective tissue component of muscle distracted at three different rates in order to determine whether low rates of distraction would enable the connective tissue component, as well as the contractile component (number of serial sarcomeres), to adapt more completely to the increased functional length of the muscle and thus lead to improved range of joint movement. It was found that loss of range of movement varied with rate of distraction. At the low rate, there was no change in the passive tension or collagen content compared to muscles from sham-operated animals, and range of movement was significantly greater than at the other rates. At the medium rate, although the muscles showed good adaptation in terms of serial sarcomere number, passive tension and collagen content was increased and range of movement reduced, indicating that changes in the connective tissue component are important factors in loss of joint movement. In the case of muscle distracted at a high rate, failure of the muscle fibres to add on sufficient sarcomeres, combined with changes in the connective tissue, resulted in almost total loss of joint movement.

Animals↗
PubMed1999

Bochdalek diaphragmatic hernia presenting with acute gastric dilatation.

Congenital diaphragmatic hernia through the foramen of Bochdalek may present after infancy. A 21/2-year-old Malay girl presented with acute respiratory distress. Chest examination showed reduced chest expansion and decreased breath sounds on the left side. Chest radiograph showed a large "cyst" in the left chest, which was thought to be a lung cyst under tension. Tube thoracostomy resulted in clinical improvement. Results of a barium study showed that the cyst perforated by the thoracostomy tube was the stomach, which had herniated through a Bochdalek diaphragmatic defect. Surgical repair of the diaphragmatic defect and closure of the perforated stomach was performed successfully. Congenital diaphragmatic hernia should be included in the differential diagnosis of respiratory distress in young children. Nasogastric tube placement must be considered as an early diagnostic or therapeutic intervention when the diagnosis is suspected.

Child, Preschool↗